1. Field of the Invention
This invention relates to 4-isoxazolecarboxamide derivatives and their pharmaceutically acceptable salts, particularly those derivatives which are substituted at the 3-position by a carboxylic acid group or ester and at the 5-position by a lower alkyl group. These compounds are useful in treating inflammation, autoimmune disease, allograft rejection or graft-versus-host rejection in mammals. This invention also relates to pharmaceutical compositions containing such compounds.
2. Related Disclosures
U.S. Pat. No. 4,284,786 (Hoechst AG) discloses the compound of the formula: ##STR2## namely, 5-methyl-N-(4-trifluoromethylphenyl)-4-isoxazolecarboxamide, also known as HWA-486, which is disclosed as being useful as an antirheumatic, antiphlogistic, antipyretic and analgesic agent, and for the treatment of multiple sclerosis. U.S. Pat. No. 4,351,841 discloses a method of using HWA-486 in the treatment of inflammation, rheumatism or multiple sclerosis, and West German Offenlegungsschrift 35 34 440 (Hoechst AG) discloses using HWA-486 in the treatment of graft-versus-host diseases and autoimmune diseases.
U.S. Pat. No. 4,087,535 (Hoechst AG) discloses compounds of the formula: ##STR3## wherein each of R.sup.1, R.sup.2 and R.sup.3 can be hydrogen, halo, or optionally substituted lower alkoxy or lower alkyl. These compounds are disclosed as being useful as anti-inflammatory and analgesic agents.
European Published Patent Application No. 0 259 972 (Lilly) discloses compounds of the formula: ##STR4## wherein each of R.sup.1 and R.sup.2 can be hydrogen or lower alkyl; each of R.sup.3, R.sup.4, R.sup.5 and R.sup.6 can be hydrogen, hydroxy, halogen, nitro, cyano, lower alkyl, lower alkoxy, lower haloalkyl, lower haloalkoxy; and Y is a 5- or 6-membered heterocyclic ring excluding pyrazole. These compounds are disclosed as being useful in treating immune diseases such as arthritis and for treating diseases in which leukotrienes are implicated.
The disclosures of these and all other documents referred to in this specification are incorporated herein in whole by reference.